Methotrexate, doxorubicin, and cisplatinum regimen is still the preferred option for osteosarcoma chemotherapy: A meta-analysis and clinical observation

Abstract

Background: We designed the study to investigate whether methotrexate, doxorubicin, and cisplatinum (MAP) chemotherapy strategy was still the preferred option for the survival of osteosarcoma patients.

Method: We collected some trials of osteosarcoma to make a meta-analysis first. Then, we retrospectively collected data from 115 patients with osteosarcoma and performed further analysis to verify the impact of MAP regimen on the survival of patients.

Results: Seven studies including 3433 participants met the preliminary inclusion criteria. Meta-analysis of the 3-year disease-free survival (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 0.88-1.28; P = .52) and overall survival (OR = 1.21, 95% CI: 0.70-2.11; P = .54), 5-year disease-free survival (OR = 1.07, 95% CI: 0.87-1.30; P = .54) and overall survival (OR = 0.86, 95% CI: 0.65-1.12; P = .26), and mortality rate (OR = 0.90, 95% CI: 0.70-1.17; P = .44), showed no statistically significant differences. The most common grade 3/4 adverse events were neutropenia (498 [85.9%] patients in MAP vs 533 [93.3%] in MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs [MAP]). MAP was associated with less frequent toxicities than MAP group with statistical significance in thrombocytopenia, febrile neutropenia, anemia, and hypophosphatemia. The same phenomenon could also be seen in the analysis of clinical data.

Conclusion: MAP regimen remains the preferred option for osteosarcoma chemotherapy.

Figure 1

Meta-analysis of survival rate between MAP and other chemotherapy strategies. (A) Forest plot (RE) of 3-year EFS rates between MAP and other chemotherapy strategies. (B) Forest plot (RE) of 3-year OS rates between MAP and other chemotherapy strategies. (C) Forest plot (RE) of 5-year EFS rates between MAP and other chemotherapy strategies. (D) Forest plot (RE) of 5-year OS rates between MAP and other chemotherapy strategies. (E) Forest plot (RE) of mortality rates between MAP and other chemotherapy strategies. EFS = event-free survival, FE = fixed effect, MAP⁺ = MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs, MAP = methotrexate + doxorubicin + cisplatinum, OR = odds ratio, OS = overall survival, RE = random effect, RR = risk ratio.

Figure 2

Meta-analysis of all kinds of toxicity rates among chemotherapy strategies. (A) Forest plot (RE) of grade 3/4 neutropenia incidence rates between MAP and other chemotherapy strategies. (B) Forest plot (RE) of grade 3/4 thrombocytopenia incidence rates between MAP and other chemotherapy strategies. (C) Forest plot (RE) of grade 3/4 febrile neutropenia incidence rates between MAP and other chemotherapy strategies. (D) Forest plot (RE) of cardiac toxicity incidence rates between MAP and other chemotherapy strategies. (E) Forest plot (RE) of grade 3/4 anemia incidence rates between MAP and other chemotherapy strategies. (F) Forest plot (RE) of grade 3/4 hypophosphatemia incidence rates between MAP and other chemotherapy strategies. (G) Forest plot (RE) of grade 3/4 mucositis incidence rates between MAP and other chemotherapy strategies. (H) Forest plot (RE) of grade 3/4 infection incidence rates between MAP and other chemotherapy strategies. EFS = event-free survival, FE = fixed effect, MAP⁺ = MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs, MAP = Methotrexate + doxorubicin + cisplatinum, OR = odds ratio, OS = overall survival, RE = random effect, RR = risk ratio.

Figure 3

Kaplan–Meier curve of overall survival for 115 patients. (A) Kaplan–Meier curve of overall survival by metastases status at registration. (P1 = .000 [without metastasis vs lung metastasis]; P2 = .000 [without metastasis vs brain metastasis] P3 = .000 [without metastasis vs other metastasis]). (B) Kaplan–Meier curve of overall survival by treatment regimens. (PST = palliative supportive treatment; P1 = .151 [MAP vs MAP+]; P2 = .000 [MAP vs PST]; P3 = .000 [MAP⁺ vs PST]). EFS = event-free survival, FE = fixed effect, MAP⁺ = MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs, MAP = methotrexate + doxorubicin + cisplatinum, OR = odds ratio, OS = overall survival, PST = palliative supportive treatment, RE = random effect, RR = risk ratio.